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Effect of Carica papaya on IRS-1/Akt Signaling Mechanisms in High-Fat-Diet-Streptozotocin-Induced Type 2 Diabetic

Jeane Rebecca Roy1, Coimbatore Sadagopan Janaki1, Selvaraj Jayaraman2

  • 1Department of Anatomy, Bhaarath Medical College and Hospital, Bharath Institute of Higher Education and Research (BIHER), Chennai 600 073, Tamil Nadu, India.

Nutrients
|October 14, 2022
PubMed

Insights

Carica papaya extract improves type 2 diabetes (T2DM) by regulating key enzymes and enhancing insulin signaling pathways (IRS-1/Akt) in skeletal muscle. This study identifies trans-ferulic acid as a potential bioactive compound.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Metabolic Diseases

Background:

  • Insulin resistance in skeletal muscle is a primary driver of type 2 diabetes (T2DM), often preceding clinical diagnosis.
  • While Carica papaya (C. papaya) shows antidiabetic potential, its specific molecular mechanisms, particularly involving insulin receptor substrate-1 (IRS-1)/Akt signaling, remain unclear.

Purpose of the Study:

  • To investigate the effect of C. papaya on IRS-1 and Akt signaling in a rat model of T2DM.
  • To identify bioactive compounds in C. papaya that interact with IRS-1 and Akt using in silico analysis.

Main Methods:

  • Rats were induced with T2DM using a high-fat diet and streptozotocin.
  • Ethanolic C. papaya leaf extract (600 mg/kg) was administered for 45 days.
  • Evaluated gluconeogenic/glycolytic enzymes, gene expression, and immunohistochemistry of IRS-1 and Akt in skeletal muscle.
  • Performed in silico analysis to assess interactions between C. papaya compounds and IRS-1/Akt proteins.

Main Results:

  • C. papaya treatment normalized gluconeogenic and glycolytic enzyme levels in diabetic rat skeletal muscle.
  • The extract significantly modulated the expression of IRS-1 and Akt in skeletal muscle.
  • In silico analysis revealed trans-ferulic acid as a potent inhibitor against IRS-1 and Akt targets.

Conclusions:

  • C. papaya effectively restores normoglycemia in T2DM by enhancing IRS-1 and Akt expression in skeletal muscle.
  • Trans-ferulic acid is identified as a key bioactive compound in C. papaya responsible for these beneficial effects.
  • This research elucidates a molecular mechanism for C. papaya's antidiabetic action, highlighting its therapeutic potential.
Keywords:
AktCarica papayainsulin receptor substrate-1insulin signalingmolecular dynamicsskeletal muscle

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